Transcriptomic analysis uncovers novel synergistic mechanisms in combination therapy for lupus nephritis

Kidney International
Jia FuZhihong Liu

Abstract

A recent clinical study showed that combination therapy consisting of mycophenolate mofetil, tacrolimus and steroids was shown to be more effective in achieving complete remission in patients with severe forms of lupus nephritis than conventional therapy consisting of intravenous cyclophosphamide and steroids. To explore the underlying molecular and cellular mechanisms of increased efficacy of the combination therapy regimen, we employed a mouse model of lupus nephritis, MRL/lpr mice, and treated them with monotherapies of prednisone, mycophenolate mofetil, or tacrolimus, or with their combination. Consistent with previous clinical findings, combination therapy markedly improved renal outcome compared to the monotherapies in mice with lupus nephritis. Transcriptomic analysis of their kidneys revealed distinct molecular pathways that were differentially regulated in combination therapy versus monotherapies. Combination therapy not only provided additive immunosuppressive effects, but also induced gene expression and molecular pathways to confer enhanced renoprotection. Specifically, combination therapy inhibited TLR7 expression in the kidneys of mice with lupus nephritis; combination of tacrolimus and mycophenolate mofetil led t...Continue Reading

References

Jan 1, 1992·International Archives of Allergy and Immunology·J LiuT Tsunematsu
Mar 6, 1986·The New England Journal of Medicine·H A AustinJ L Decker
Nov 25, 2005·The New England Journal of Medicine·Ellen M GinzlerGerald B Appel
Aug 25, 2006·Kidney International·M Waldman, G B Appel
Apr 27, 2007·Journal of the American Society of Nephrology : JASN·Rahul D PawarHans-Joachim Anders
Nov 9, 2007·Kidney International·V SepeA Dal Canton
May 16, 2008·Nephron. Experimental Nephrology·Takehiko WadaStuart J Shankland
Dec 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christophe RichezIan R Rifkin
Jul 16, 2010·American Journal of Physiology. Renal Physiology·Adam GuessWilliam E Smoyer
Oct 13, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Eva SchönenbergerMario Schiffer
Nov 19, 2011·Nucleic Acids Research·Thomas KelderAlexander R Pico
Jun 23, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Celine C BerthierMatthias Kretzler
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Nov 11, 2014·Annals of Internal Medicine·Zhihong LiuMinlin Zhou
Nov 22, 2014·Current Opinion in Nephrology and Hypertension·Frank C Brosius, John Cijiang He
Apr 1, 2015·Nature Reviews. Nephrology·Chandra Mohan, Chaim Putterman
Apr 15, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Lindsay J EdwardsVasileios Kyttaris
Jul 15, 2015·Clinical Journal of the American Society of Nephrology : CJASN·Alexander C Wiseman
Sep 15, 2015·Expert Review of Clinical Immunology·Chi Chiu Mok
Oct 3, 2015·Autoimmunity Reviews·Jennifer HannahDavid D'Cruz
Nov 9, 2016·Clinical Journal of the American Society of Nephrology : CJASN·Salem AlmaaniBrad H Rovin
Aug 2, 2017·Journal of the American Society of Nephrology : JASN·Haitao ZhangZhihong Liu

❮ Previous
Next ❯

Citations

Jun 28, 2019·Lupus Science & Medicine·Evan DerChaim Putterman
Aug 16, 2018·Current Rheumatology Reports·Isabelle AyoubBrad H Rovin
Dec 13, 2018·Nature Reviews. Rheumatology·Mariele GattoAndrea Doria
May 23, 2019·Molecular Medicine Reports·Dongdong WangZhiping Li
May 30, 2019·International Journal of Molecular Sciences·Takahiro UchidaShuhji Seki
Nov 9, 2019·KI Reports·Yu AnZhihong Liu
Sep 25, 2018·Current Opinion in Immunology·Naomi I Maria, Anne Davidson
Jan 31, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Martijn van den BroekJitske Jansen
Apr 19, 2021·Journal of Nanobiotechnology·Chang Seong KimSoo Wan Kim

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved